The objective of the study is to identify the ventilatory adjustments (i.e., PCO2, pH conditions) which will promote optimum availability of oxygen to tissues in the presence of pre-existing disturbances in pulmonary gas exchange. Efforts to treat such disturbances invariably utilize hyperventilation resulting in an increased alveolar oxygen tension, which of itself does not necessarily improve oxygen delivery or cellular utilization. Newer concepts emphasize the pH dependence between oxygen tension and availability, and also the pH relationship between ventilation and body metabolic rate. Inherent in these views is that there is an optimal level of ventilation (PCO2 and pH) which will result in maximal availability of oxygen for aerobic metabolism. The relationship of the primary variables in the oxygen delivery sequence is presented and also our experimental animal protocol to examine the role of respiratory gas tensions and blood pH on these variables in order to determine the ventilatory adjustments necessary for optimal oxygenaton. We believe that the conditions for optimal oxygen delivery will require reversing the increased oxygen consumption and alkalosis associated with hyperventilaton and may be achieved at an arterial CO2 tension above 40 torr (pH less than 7.4), conditions presently associated with respiratory failure and currently treated with hyperventilation. Verification of this hypothesis will require revision of management in the critically-ill patient.